Introduction

The Food and Drug Association (FDA) regulates use of all investigational drugs and devices, including emergency use. The IRB must be notified of all emergency use, even though it is not considered research.

Definitions

Emergency Use: The FDA defines emergency use as the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval [21CFR 56.102 (d)].

Life-threatening: For the purposes of this guidance, life-threatening includes the scope of both life-threatening and severely debilitating as defined below:

• The FDA defines life-threatening as diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life threatening do not require the condition to be immediately life threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
• The FDA defines severely debilitating as diseases or conditions that cause major, irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.

Guidance

If a physician determines that the use of an investigational drug or device meets the FDA definition of life-threatening, they may contact the IRB to discuss the potential emergency use. If the definition of life-threatening is not met, emergency use procedures must not be followed. For additional options, consult the IRB guidance on Expanded Access to Investigational Drugs and Devices.

IRB Requirements

The treating physician must notify the IRB before the emergency use of a test article. If the IRB can reasonably hold a convened meeting to review all prepared emergency use materials prior to the use of the test article, it is not considered exempt from prospective review by the IRB. Physicians should submit a New Study Application which will be reviewed and approved by the convened IRB. For urgent situations, contact the IRB office 801-581-3655 to make arrangements for review at the next convened panel.

If immediate use of the test article is required to save the life of the patient and there is not sufficient time to contact the IRB, the FDA provides an emergency use provision in the regulations [21 CFR 56.104(c)] which allows an exception from prospective review by the IRB. In this case, the emergency use of the test article must be reported to the IRB as soon as possible and no later than 5 working days from the time the procedure is conducted, or drug is administered.

Notifying the IRB of the emergency use, either before or after the procedure or drug administration, should be done through the University of Utah Electronic Research Integrity and Compliance Administration system (ERICA) using the Emergency Use of a Test Article Application which offers both:

• Proposed Emergency Use – used to notify the IRB in advance when a test article must be used in an emergency and convened IRB cannot meet beforehand
• Reported Emergency Use – used to report to the IRB after a patient was treated immediately, in an emergency. This must be reported within 5 business days after the emergency use treatment

Notifying the IRB using the Emergency Use of a Test Article Application is not IRB approval. A letter will be issued from the IRB Chair, Co-Chair or Vice-Chair stating whether the use complies with the regulatory requirements.

Informed Consent

Even for emergency use, the treating physician must obtain informed consent from the patient or their legally authorized representative. An informed consent must be submitted to the IRB. The drug/device manufacturer may offer a consent template, but it must state that the treatment is not FDA-approved, is an option for treating the patient’s life-threatening condition, and is not part of research. Physicians should use the Emergency Use Consent Checklist to ensure all required elements and standard language are included.

Additionally, the FDA provides an exception from the requirements of informed consent [21 CFR 50.23] as outlined below. Before the use of the test article, both the treating physician and a physician who is not otherwise participating in the clinical investigation must certify all of the following:

1. The human subject is confronted by a life-threatening situation necessitating use of test article.
2. Consent cannot be obtained because of an inability to communicate with or obtain consent from the subject.
3. Time is not sufficient to obtain consent from subject’s legal representative.
4. No alternative generally approved method is available.
5. If immediate use of the test article is required to save the life of the subject and time is not sufficient to obtain independent determination by another physician, a determination by the treating physician shall be made. This determination is to be reviewed and evaluated in writing by a physician who is not participating in the investigation within 5 days after use of article. Complete the Emergency Use of a Test Article Without Consent Physician Certification and attach it to the Emergency Use of a Test Article Application in ERICA.

The documentation described above must be submitted to the IRB within 5 working days after the use of a test article.

IRB Determination

The Emergency Use of a Test Article Application will be evaluated. An informed consent document or the Emergency Use of a Test Article Without Consent Physician Certification must be included.

• If the IRB Chair concurs that the proposed or reported activity meets the FDA requirements for exemption from prospective IRB review for emergency use of a test article, the treating physician will receive an acknowledgment via email from ERICA.
• If the IRB Chair determines that there is time to review a proposed use of the test article (i.e. the test article has not been used yet) at the convened IRB, the physician will be required to complete the full new study application, and the application will not be considered for the exemption from prospective IRB review for emergency use.
• If the IRB Chair determines that a reported use of the test article (i.e. the test article has already been used) does not meet the definition of emergency use, the physician will be required to submit a protocol deviation and the IRB will review the use for non-compliance.

Is the emergency use of a test article considered “research?”

Emergency use of a test article (21 CFR 56.104(c)) meets the FDA definition of clinical investigation and requires regulation under the Food, Drug and Cosmetic Act. It also involves the administration of a test article to a human, so it involves human subjects. Therefore, under FDA regulations, it is human research.

The research must not be subject to DHHS regulation since DHHS has no corresponding exemption from prospective IRB review. The activity must not meet the DHHS definition of “research” and involve “subjects” as defined by DHHS regulations. In other words, the data from emergency use may not be reported in a way that implies that the activity was a prospectively planned systematic investigation designed to develop or contribute to generalizable knowledge.

Emergency Use of an Investigational Drug

The emergency use of an unapproved investigational drug or biologic requires an Investigational New Drug (IND) number. When a physician submits the Emergency Use of a Test Article application in ERICA, an IND number must be provided. See the Points to Consider section below for additional information that will be required with your submission

The physician must either obtain an emergency use IND number from the FDA or obtain access to the drug under an existing IND number. The IND holder (usually the drug manufacturer) must authorize the drug to be used under the emergency use regulations, which may require contacting the FDA. For more information, please refer directly to the FDA guidance, Emergency Use of an Investigational Drug or Biologic – Information Sheet.

Emergency Use of an Unapproved Device

Emergency use is when there is a need to use a device that has not received the FDA’s approval or clearance in an emergency. An unapproved device should normally only be used in human subjects if it is approved for clinical testing under an IDE and if it is used by an investigator for the sponsor in accordance with the terms and conditions of the application. Emergency use of an unapproved device, however, may also occur when: (i) an IDE for the device does not exist, (ii) when a physician wants to use the device in a way not approved under the IDE, or (iii) when a physician is not an investigator under the IDE.

A physician who intends to treat a patient with an unapproved medical device in an emergency situation should conclude that:

1. The patient has a life-threatening condition that needs immediate treatment;
2. No generally acceptable alternative treatment for the condition exists; and
3. Because of the immediate need to use the device, there is no time to use existing procedures to get FDA approval for the use.

The FDA expects the physician to make the determination that the patient’s circumstances meet the above criteria, to assess the potential for benefit from the use of the unapproved device, and to have substantial reason to believe that benefits will exist.

If using an unapproved medical device, the physician must obtain authorization from the IDE sponsor if an IDE exists for the device. Review the Points to Consider below for documentation that will be required with your submission including authorization from the device manufacturer.

The emergency use of an investigational device must be reported to the FDA by the IDE sponsor within 5 working days. If no IDE exists, the physician should report the emergency use to the FDA.

Documents and References

FDA Guidance: Expanded Access for Medical Devices, Emergency Use

FDA Guidance: Emergency Use of an Investigational Drug or Biologic – Information Sheet

IRB SOP 506: Emergency Use of a Test Article

University of Utah IRB Emergency Use Consent Checklist

University of Utah IRB Emergency Use of a Test Article without Consent Physician Certification 

Points to Consider